The partial coherence method for assessment of impaired cerebral autoregulation using near- infrared spectroscopy: potential and limitations

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The partial coherence method for assessment of impaired cerebral autoregulation using near- infrared spectroscopy: potential and limitations

D. De Smet

¹

, J. Jacobs

¹

, L. Ameye

¹

, J. Vanderhaegen

²

, G. Naulaers

²

, P.

Lemmers

³

, F. van Bel

³

, M. Wolf

⁴

, and S. Van Huffel

¹

.

1

Dept. of Electrical Engineering (ESAT), SCD Division, Katholieke Universiteit Leuven, Belgium. Address correspondence to S. Van Huffel, prof. dr. ir., ESAT/SCD, Kasteelpark Arenberg 10/2446, 3001 Leuven, Belgium. E-mail: sabine.vanhuffel@esat.kuleuven.be

2

Dept. of Neonatology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium,

3

Dept. of Neonatology, Wilhelmina Children's Hospital, Utrecht, The Netherlands,

4

Clinic of Neonatology, University Hospital Zurich, Switzerland

Abstract The most important forms of brain injury in premature infants are partly caused by disturbances in cerebral autoregulation. As changes in cerebral intravascular oxygenation (HbD), regional cerebral oxygen saturation (rSO

2

), and cerebral tissue oxygenation (TOI) reflect changes in cerebral blood flow (CBF), impaired autoregulation can be measured by studying the concordance between HbD/rSO

2

/TOI and the mean arterial blood pressure (MABP), assuming no changes in oxygen consumption, arterial oxygen saturation (SaO

2

), and in blood volume. We investigated the performance of the partial coherence (PCOH) method, and compared it with the coherence method (COH). The PCOH method allows to eliminate in a linear way the influence of SaO

2

on HbD/rSO

2

/TOI. We started from long-term recordings measured in the first days of life simultaneously in 30 infants from three medical centres. We then compared the COH and PCOH results with patient clinical characteristics and outcomes, and concluded that PCOH might be a better method for assessing impaired autoregulation.

1 Introduction

In this study in preterm infants, NIRS is used to measure cerebral autoregulation

over long periods, reflecting static autoregulation. The use of NIRS for this

purpose was shown by Tsuji et al. (2000). Changes in HbD, rSO

2

, or TOI reflect

changes in CBF and the correlation between MABP and HbD/rSO

2

/TOI is a

reflection of autoregulation. A good correlation was found between autoregulation

and outcome, i.e. frequency of severe intraventricular bleedings. rSO

2

and TOI are

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both absolute values, they are less prone to movement artefacts than HbD, and easier to measure in clinical practice.

We studied the concordance between HbD/rSO

2

/TOI and MABP by means of the coherence (COH, measuring the degree of linear dependence between the frequency spectra of two signals), and partial coherence (PCOH) (Leuridan et al.

1985) coefficients. The latter one allows the elimination of the linear influence of one signal on another one. This means that, in contrast to COH, PCOH can also be applied in periods of fluctuating SaO

2

thereby improving the automation and the use of the method. We developed and investigated four PCOH algorithms fixing the physiological interactions between SaO

2

, MABP, and HbD/rSO

2

/TOI. We studied the PCOH properties in particular during periods of fluctuating SaO

2

. For this purpose we used parameters that synthesize patient level of autoregulation:

the mean score (mCOH and mPCOH) (Tsuji et al. 2000), the pressure-passive index (PPI) (Soul et al. 2007), and the critical percentage of the recording time (CPRT) (De Smet et al. 2008). Finally, we compared these parameters with the infant clinical characteristics and outcomes: infant post menstrual age (PMA, in weeks), birth weight (BW, in g), Bayley's psychomotor (PDI) and mental (MDI) developmental indices after 9, 18, and 24 months (for the Leuven, Zurich, and Utrecht data respectively), Griffith developmental index (combination of a mental and psychomotor test) after 24 months, and APGAR score at birth and 5 minutes after birth.

2 Datasets

Thirty premature infants with need for intensive care were monitored, among whom 10 from the University Hospital Zurich (Switzerland), 10 from the University Medical Centre Utrecht (The Netherlands), and 10 from the University Hospital Leuven (Belgium). SaO

2

was measured continuously by pulse oxymetry, and MABP by an indwelling arterial catheter. Transcranial NIRS signals HbD (measured by the Critikon Cerebral Oxygenation Monitor 2001), rSO

2

(INVOS4100, Somanetics Corp.), and TOI (NIRO300, Hamamatsu) were measured for non-invasive monitoring of cerebral oxygenation. The signals were measured simultaneously in the first days of life. For the Zurich data, the babies were characterized by a mean PMA of 28 1/7 weeks (std=2 1/7) and a mean BW of 1198g (std=439). For the Utrecht data, the babies were characterized by a mean PMA of 29 2/7 weeks (std=1 2/7) and a mean BW of 1130.67g (std=311.36). For the Leuven data, the babies were characterized by a mean PMA of 28 5/7 weeks (std=3 2/7) and a mean BW of 1125g (std=503.76). HbD, rSO

2

, and TOI were recorded digitally on a personal computer at a sampling frequency of 1.677Hz, 1Hz, and 10Hz for the Zurich, Utrecht, and Leuven data, respectively. Afterwards the signals from all datasets were downsampled to the smallest frequency multiple of the recording frequencies i.e. 0.333Hz (periodicity: 3s) to ensure comparability.

A preprocessing algorithm was applied to the recordings of all centres to remove

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signal artefacts. Each artefact point was simply deleted from the recording for each signal (Soul et al. 2007). Among the preprocessing operations, we kept all variables within normal ranges, in particular SaO

2

in the range 80-100%.

3 Methods

Since the possible concordance between MABP and the NIRS signals varies with time, we computed COH and PCOH over successive half-overlapping epochs of duration 10, 15, and 12.5 minutes for the Zurich, Utrecht, and Leuven data, respectively. The average of COH and PCOH over the frequency band 0.0033- 0.04Hz (corresponding to phenomena of duration in the range 25-300s) (Soul et al.

2007) was used as score for the considered epoch. The epoch durations were computed from the calibration of the mean COH (for all patients of each center) on the mean absolute-valued correlation coefficient (COR), to be sure that the score value of 0.5 could be considered as critical (it suggests a relation between the signals based on 50% shared variance) (de Boer et al. 1985). If mCOH or mPCOH was higher than this critical score value (CSV), the infant was said to have an impaired cerebral autoregulation. We built the PCOH algorithms from the supposed physiological models fixing the interactions between the measured signals as follows:

 SaO

2

= i(SaO

2

) + f(MABP)

 MABP = i(MABP) + f(SaO

2

)

 NIRS = i(NIRS) + f(MABP) + f(SaO

2

)

where i(...) represents the independent part of the signal, f(...) stands for is a function of, and NIRS represents HbD, rSO

2

, or TOI. The algorithms are:

 PCOH1 = COH(MABP - SaO

2

, NIRS - SaO

2

)

 PCOH2 = COH(MABP , NIRS - SaO

2

)

 PCOH3 = COH(MABP - i(SaO

2

) , NIRS - i(SaO

2

))

 PCOH4 = COH(MABP , NIRS - i(SaO

2

))

where COH(… , …) is the coherence computed between both signals. For all patients we studied th e performances of PCOH compared to COH on a global basis, but we also looked in detail at epochs with fluctuating SaO

2

and compared the results when using extra raw (non preprocessed) data.

4 Results

When considering all patients, we saw a trend of higher mPCOHs as compared

to mCOH. In addition the CPRTs and PPIs of PCOH were generally higher as

compared to the CPRT and PPIs of COH. PCOH3 shows a higher mPCOH,

CPRT, and PPI than the other PCOH algorithms, and than PCOH2 which shows

the lowest values. For more details we refer to tables 1 to 3. We also considered

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patients for whom the oxygen fraction of the inhibited air has been intentionally modified. We particularly concentrated on epochs with a high variance in SaO

2

. In these epochs, mean scores were significantly higher with PCOH3 as the highest. More details are given in Table 4 and Fig. 1.

mPCOH3 detects a fewmore patients with impaired autoregulation than mCOH and the other mPCOHs. The CPRT and PPI10 (with confidence level α=0.1) detects many more patients with impaired autoregulation than mCOH and mPCOHs, and approximatively two times more patients than PPI5 (α=0.05).

Patients with mCOH and mPCOHs > 0.5 have a slightly lower mean PMA and BW than the overall average. High PCOH values (m>0.5, CPRT>0, PPI>0) better detect bad clinical outcome than COH (MDI<84, PDI<84, Apgar<7). CPRT and PPI10 better detect bad clinical outcome than mean score values.

5 Discussion

It is important to remind that COH and PCOH are measurements of impaired cerebral autoregulation, and that the considered clinical patient characteristics witness a possible brain damage. In the literature an evident correlation between impaired autoregulation and brain damage in neonates has been described. And this is what we assume in this study. We looked for the method that best fits the occurrences of brain damage. Our results indicate that (1) the PCOH score is more accurate in detecting infants with brain malfunctions as compared to the COH method; (2) PCOH3 has the highest accuracy in detecting impaired autoregulation.

Particularly, the CPRT and PPI10 -computed from the COH and PCOH scores- detect more than 50% of all infants with bad clinical outcomes. These observations rather indicate that PCOH highlights more cases of impaired autoregulation as compared to COH, and does not necessarily mean that PCOH indicates a better fit between patients with impaired autoregulation and patients with bad clinical outcome. However, we should remark that in this study the patient characteristics and outcomes are not available for all patients whereas further statistical analysis on larger multicentre datasetsare needed

We expected the PCOH4 model to be more realistic than the PCOH3 method, because SaO

2

showed to have an influence on MABP only in those recordings with changes in SaO

2

that were deliberately provoked by modifying the inspired oxygen fraction. Nevertheless this could not be confirmed by our results.

Furthermore, a lack of concordance with patient neurological outcomes could also be explained by the fact that COH (and consequently PCOH) only measures the linear and stationary concordance between MABP and the NIRS-measured signals, or by the fact that PCOH assumes a linear dependency between the considered signals.

In conclusion, as HbD/rSO

2

/TOI are often considered as surrogate of CBF,

impaired autoregulation can be assessed by quantifying the concordance between

these signals and MABP. Being able to eliminate the influence of other signals as

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SaO

2

, the partial coherence method was shown to perform better than the classical coherence method.

Acknowledgments The research was supported by: Research Council KUL: GOA AMBioRICS, CoE EF/05/006, by FWO projects G.0519.06 (Noninvasive brain oxygenation), and G.0341.07 (Data fusion), by Belgian Federal Science Policy Office IUAP P5/22.

References

1. de Boer R, Karemaker J, Strackee J (1985) Relationships between short-term blood-pressure fluctuations and heart-rate variability in resting subjects, I: a spectral analysis approach. Med Biol Eng Comput 23:352–358

2. De Smet D, Vanderhaegen J, Naulaers G et al (2008) New measurements for assessment of impaired cerebral autoregulation using near-infrared spectroscopy. Proc of the 2007 ISOTT conf, Uppsala (Sweden), to be published in 2008

3. Leuridan J, Rost B (1985) Multiple input estimation of frequency response functions: diagnostic techniques for the excitation. ASME 85-DET-107

4. Soul J, Hammer P, Tsuji M et al (2007) Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants. Pediatr Res 61(4):467-473

5. Tsuji M, Saul J, du Plessis A et al (2000) Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatr Rev 106(4):625-632

Table 1 Mean score, standard deviation (std), critical percentage of the recording time (CPRT), and pressure-passive index (PPI) with confidence level α=0.1 of the Leuven data. The numbers below are averages on the ten infants from Leuven.

Leuven COH PCOH1 PCOH2 PCOH3 PCOH4

Mean 0.39 0.41 0.41 0.44 0.42

Std 0.09 0.1 0.09 0.12 0.1

CPRT 14% 20% 14% 27% 22%

PPI10 10.64% 12.40% 11.60% 18.35% 17.02%

Table 2 Mean score, standard deviation, CPRT, and PPI10 of the Utrecht data. The numbers below are averages on the ten infants from Utrecht..

Utrecht COH PCOH1 PCOH2 PCOH3 PCOH4

Mean 0.35 0.34 0.33 0.39 0.36

Std 0.09 0.09 0.09 0.1 0.09

CPRT 13% 11% 8% 22% 17%

PPI10 20.80% 19.30% 15.10% 28.16% 21.45%

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Table 3 Mean score, standard deviation, CPRT, and PPI10 of the Zurich data. The numbers below are averages on the ten infants from Zurich.

Zurich COH PCOH1 PCOH2 PCOH3 PCOH4

Mean 0.57 0.61 0.57 0.63 0.63

Std 0.09 0.1 0.09 0.12 0.12

CPRT 72% 75% 70% 80% 71%

PPI10 17.02% 34.02% 19.27% 40.06% 29.04%

Table 4 Local analysis: the oxygen fraction inhibited by the infant has, in some Zurich patients, intentionally been modified to create locally a high variance in SaO

2

. The table contains the overall score means of such a patient, and the means related to the epoch of high SaO

2

variance (20-40min). Please see also Fig. 1.

Zurich mCOH mPCOH1 mPCOH2 mPCOH3 mPCOH4 stdSaO2

Overall 0.55 0.52 0.52 0.61 0.57 1.2

20-40 0.64 0.51 0.61 0.75 0.73 2.51

Fig. 1 Local analysis: the oxygen fraction inhibited by the infant has, in some Zurich patients,

intentionally been modified to create locally a high variance in SaO

2